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WNK4 Gene

protein-coding   GIFtS: 64
GCID: GC17P040932

WNK Lysine Deficient Protein Kinase 4

(Previous names: protein kinase, lysine deficient 4)
(Previous symbol: PRKWNK4)
  See WNK4-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
WNK Lysine Deficient Protein Kinase 41 2     PHA2B2 5
PRKWNK41 2 3 5     Protein Kinase, Lysine Deficient 41
Protein Kinase Lysine-Deficient 42 3     Serine/Threonine-Protein Kinase WNK42
Protein Kinase With No Lysine 42 3     EC 2.7.118
EC 2.7.11.13 8     

External Ids:    HGNC: 145441   Entrez Gene: 652662   Ensembl: ENSG000001265627   OMIM: 6018445   UniProtKB: Q96J923   

Export aliases for WNK4 gene to outside databases

Previous GC identifers: GC17P038188 GC17P036697


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for WNK4 Gene:
This gene encodes a member of the WNK family of serine-threonine protein kinases. The kinase is part of the tight
junction complex in kidney cells, and regulates the balance between NaCl reabsorption and K(+) secretion. The
kinase regulates the activities of several types of ion channels, cotransporters, and exchangers involved in
electrolyte flux in epithelial cells. Mutations in this gene result in pseudohypoaldosteronism type IIB.(provided
by RefSeq, Sep 2009)

GeneCards Summary for WNK4 Gene:
WNK4 (WNK lysine deficient protein kinase 4) is a protein-coding gene. Diseases associated with WNK4 include pseudohypoaldosteronism type iib, and pseudohypoaldosteronism type ii. GO annotations related to this gene include protein serine/threonine kinase activity. An important paralog of this gene is WNK1.

UniProtKB/Swiss-Prot: WNK4_HUMAN, Q96J92
Function: Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell
signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride
cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D,
SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by
phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel,
KCNJ1, via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by
clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl
reabsorption and K(+) secretion to maintain integrated homeostasis. Phosphorylates NEDD4L

Gene Wiki entry for WNK4 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000017.10  NT_010783.16  NC_018928.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the WNK4 gene promoter:
         STAT1   Pax-5   SREBP-1c   STAT1beta   CUTL1   STAT1alpha   SREBP-1b   Roaz   SREBP-1a   RSRFC4   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidWNK4 promoter sequence
   Search Chromatin IP Primers for WNK4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat WNK4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q21-q22   Ensembl cytogenetic band:  17q21.31   HGNC cytogenetic band: 17q21-q22

WNK4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
WNK4 gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17P040932:  view genomic region     (about GC identifiers)

Start:
40,932,649 bp from pter      End:
40,949,084 bp from pter
Size:
16,436 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: WNK4_HUMAN, Q96J92 (See protein sequence)
Recommended Name: Serine/threonine-protein kinase WNK4  
Size: 1243 amino acids; 134739 Da
Cofactor: Magnesium (By similarity)
Subunit: Interacts with the C-terminal region of KCNJ1 (By similarity). Interacts with WNK1 and WNK3 (By
similarity). Interacts with KLHL3
Caution: Cys-203 is present instead of the conserved Lys which is expected to be an active site residue. Lys-186
appears to fulfill the required catalytic function
Sequence caution: Sequence=BAC04669.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Sequence=CAC48387.1; Type=Frameshift; Positions=4;
3 PDB 3D structures from and Proteopedia for WNK4:
2V3S (3D)        4CH9 (3D)        4CHB (3D)    
Secondary accessions: Q8N8X3 Q8N8Z2 Q96DT8 Q9BYS5
Alternative splicing: 3 isoforms:  Q96J92-1   Q96J92-2   Q96J92-3   (No experimental confirmation available. Incomplete sequence)

Explore the universe of human proteins at neXtProt for WNK4: NX_Q96J92

Explore proteomics data for WNK4 at MOPED

Post-translational modifications: 

  • Phosphorylated by WNK1 and WNK3 (By similarity)1
  • Ubiquitinated by the BCR(KLHL3) complex, leading to its degradation and increased expression of KCNJ1 at the cell
    surface1
  • Ubiquitination2 at Lys157, Lys175, Lys186, Lys226, Lys241, Lys328, Lys387, Lys393, Lys450, Lys454,
                                 Lys1010, Lys1144, Lys1157, Lys1158
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for WNK4 (Q96J92) (see all 10)
     EYPYSEC  ILHRDLK  EIGRGSF  FGMCMLEM 


    See WNK4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_115763.2  
    ENSEMBL proteins: 
     ENSP00000246914   ENSP00000467088   ENSP00000467312  
    Reactome Protein details: Q96J92

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: WNK lysine deficient protein kinase 4
    Wnk family

    4 InterPro protein domains:
     IPR011009 Kinase-like_dom
     IPR008271 Ser/Thr_kinase_AS
     IPR000719 Prot_kinase_dom
     IPR024678 Kinase_OSR1/WNK_CCT

    Graphical View of Domain Structure for InterPro Entry Q96J92

    ProtoNet protein and cluster: Q96J92

    UniProtKB/Swiss-Prot: WNK4_HUMAN, Q96J92
    Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily
    Similarity: Contains 1 protein kinase domain


    Find genes that share domains with WNK4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: WNK4_HUMAN, Q96J92
    Function: Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell
    signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride
    cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D,
    SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by
    phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel,
    KCNJ1, via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by
    clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl
    reabsorption and K(+) secretion to maintain integrated homeostasis. Phosphorylates NEDD4L
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Enzyme regulation: Activation requires autophosphorylation of Ser-335. Phosphorylation of Ser-331 also promotes
    increased activity (By similarity)

         Enzyme Numbers (IUBMB): EC 2.7.11.11 2 EC 2.7.112

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity ----
    GO:0004674protein serine/threonine kinase activity ISS--
    GO:0004713protein tyrosine kinase activity ----
    GO:0005515protein binding IPI17721439
    GO:0005524ATP binding ISS--
         
    Find genes that share ontologies with WNK4           About GenesLikeMe


    Phenotypes:
         4 GenomeRNAi human phenotypes for WNK4:
     Increased cell death HMECs cel  Increased cell spreading  Increased colony dispersion (i  Upregulation of Wnt/beta-caten 

         4 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Wnk4):
     cardiovascular system  homeostasis/metabolism  no phenotypic analysis  renal/urinary system 

    Find genes that share phenotypes with WNK4           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for WNK4: Wnk4tm2.1Suc Wnk4tm1Pfi

       genOway: Develop your customized and physiologically relevant rodent model for WNK4

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    miRTarBase miRNAs that target WNK4:
    hsa-mir-296-5p (MIRT004559)

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    Selected qRT-PCR Assays for microRNAs that regulate WNK4 (see all 11):
    hsa-miR-140-5p hsa-miR-502-5p hsa-miR-563 hsa-miR-26b* hsa-miR-1291 hsa-miR-380* hsa-miR-654-5p hsa-miR-1207-3p
    SwitchGear 3'UTR luciferase reporter plasmidWNK4 3' UTR sequence
    Inhib. RNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    WNK4_HUMAN, Q96J92: Cell junction, tight junction (By similarity). Note=Present exclusively in intercellular
    junctions in the distal convoluted tubule and in both the cytoplasm and intercellular junctions in the cortical
    collecting duct. WNK4 is part of the tight junction complex (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus2
    plasma membrane2
    cytosol1
    extracellular1
    peroxisome1

    Gene Ontology (GO): 2 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm IEA--
    GO:0005923tight junction ISS--

    Find genes that share ontologies with WNK4           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for WNK4 About    
    See pathways by source

    SuperPathContained pathways About
    1Ion channel transport
    Ion channel transport0.58
    Stimuli-sensing channels0.58
    2Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds
    Transmembrane transport of small molecules0.47
    3Cell adhesion Integrin mediated cell adhesion and migration
    Cell adhesion Tight junctions0.33
    4PI3K / Akt Signaling
    PI3K / Akt Signaling
    5Diuretics Pathway, Pharmacodynamics
    Diuretics Pathway, Pharmacodynamics


    Find genes that share SuperPaths with WNK4           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 Cell Signaling Technology (CST) Pathway for WNK4
        PI3K / Akt Signaling

    1 GeneGo (Thomson Reuters) Pathway for WNK4
        Cell adhesion Tight junctions

    1 Reactome Pathway for WNK4
        Stimuli-sensing channels

    1 PharmGKB Pathway for WNK4
        Diuretics Pathway, Pharmacodynamics

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for WNK4
    Interactions:

        GeneGlobe Interaction Network for WNK4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 20)

    Selected Interacting proteins for WNK4 (Q96J921, 2, 3 ENSP000002469144) via UniProtKB, MINT, STRING, and/or I2D (see all 59)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    OXSR1O957471, 2, 3, ENSP000003117134EBI-766352,EBI-620853 MINT-5207699 MINT-5207631 MINT-5207540 MINT-5207597 MINT-5207682 MINT-5207580 MINT-5207648 MINT-5207716 MINT-5207665 MINT-5207614 MINT-5207558 I2D: score=1 STRING: ENSP00000311713
    YWHAQP273482, 3, ENSP000002380814MINT-7900157 I2D: score=1 STRING: ENSP00000238081
    ESR2Q927313, ENSP000003439254I2D: score=1 STRING: ENSP00000343925
    STK39Q9UEW83, ENSP000003482784I2D: score=3 STRING: ENSP00000348278
    SLC12A3P550173, ENSP000002625024I2D: score=1 STRING: ENSP00000262502
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006468protein phosphorylation ISS--
    GO:0006811ion transport ISS--
    GO:0006821chloride transport IEA--
    GO:0008104protein localization IEA--
    GO:0035556intracellular signal transduction ISS--

    Find genes that share ontologies with WNK4           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for WNK4

    4 HMDB Compounds for WNK4    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    ChlorineCl2 (see all 13)16887-00-6--
    MagnesiumMagnesium (see all 2)7439-95-4--

    9 Novoseek inferred chemical compound relationships for WNK4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    thiazide 71 2 15639021 (1), 17975670 (1)
    lysine 68.9 19 15639021 (2), 14769928 (2), 14616768 (1), 19706464 (1) (see all 11)
    nacl 59.7 18 15841204 (2), 19401467 (2), 15796898 (2), 16820787 (1) (see all 13)
    threonine 58 3 19690383 (1), 18547946 (1), 17647025 (1)
    potassium 55.8 14 15300163 (3), 15639021 (1), 18695394 (1), 15081430 (1) (see all 10)
    chloride 48.9 6 15300163 (3), 15639021 (1), 15637347 (1), 17194447 (1)
    serine 45.8 3 19690383 (1), 19706464 (1), 18547946 (1)
    sodium 42.1 5 18277144 (2), 15639021 (1), 18695394 (1), 19690383 (1)
    proline 39.9 2 16173916 (1), 19587141 (1)



    Find genes that share compounds with WNK4           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for WNK4 gene: 
    NM_032387.4  

    Unigene Cluster for WNK4:

    WNK lysine deficient protein kinase 4
    Hs.105448  [show with all ESTs]
    Unigene Representative Sequence: NM_032387
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000246914(uc002ibj.3 uc010wgx.2 uc002ibk.1 uc010wgy.1)
    ENST00000591448 ENST00000592669 ENST00000587705 ENST00000592072 ENST00000587745

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    Additional mRNA sequence: 

    AF390018.1 AJ309861.1 AJ316534.1 AK096003.1 AK096052.1 AK301963.1 BC136664.1 BC144356.1 

    6 DOTS entries:

    DT.91746101  DT.100022245  DT.95224531  DT.100789457  DT.92025546  DT.92052927 

    Selected AceView cDNA sequences (see all 66):

    AA513292 AL041763 CA388932 AI244885 AJ316534 AA877924 AW135316 AA687630 
    AF390018 BM683764 CA388931 AJ309861 AK096003 NM_032387 BX118400 AI650786 
    CD633905 D25718 AW082836 CD633901 CD633909 AA872586 BF000369 CD633899 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    WNK4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    WNK4 Expression
    About this image


    WNK4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Heart (Cardiovascular System)
             Atrioventricular Canal Cells Atrioventricular Canal
     
     Epithelial Cells
             Distal Tubule Cells Distal Tubule
     
     Adipose (Muscoskeletal System)
             Visceral White Adipose
     
     Kidney (Urinary System)
             Distal Tubule Cells Distal Tubule
     
     Colon (Gastrointestinal Tract)
    WNK4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    WNK4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.105448

    UniProtKB/Swiss-Prot: WNK4_HUMAN, Q96J92
    Tissue specificity: Expressed in kidney, colon and skin

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    In Situ
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for WNK4 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Wnk41 , 5 WNK lysine deficient protein kinase 41, 5 85.31(n)1
    87.55(a)1
      11 (64.51 cM)5
    698471  NM_175638.31  NP_783569.11 
     1012605675 
    chicken
    (Gallus gallus)
    Aves LOC7775801 serine/threonine-protein kinase WNK4-like 70.94(n)
    71.79(a)
      777580  XM_003642827.2  XP_003642875.2 
    lizard
    (Anolis carolinensis)
    Reptilia WNK46
    WNK lysine deficient protein kinase 4
    48(a)
    1 ↔ 1
    6(62189724-62256854)
    zebrafish
    (Danio rerio)
    Actinopterygii WNK4 (1 of 4)6
    WNK4 (3 of 4)6
    (see all 4)
    WNK lysine deficient protein kinase 4
    (see all 4)
    87(a)
    37(a)
    (see all 4)
    1 ↔ many
    1 ↔ many
    (see all 4)
    12(4246403-4257283) ENSDARG00000016381
    3(22656374-22762217) ENSDARG00000088967
    fruit fly
    (Drosophila melanogaster)
    Insecta Wnk6
    --
    14(a)
    1 → many
    3L(21536950-21548028)
    worm
    (Caenorhabditis elegans)
    Secernentea wnk-16
    Protein WNK-1, isoform l (wnk-1) mRNA, complete cd...
    19(a)
    1 → many
    IV(9200116-9212232) WBGene00006941
    rice
    (Oryza sativa)
    Liliopsida AK100930.12   -- 73.32(n)    AK100930.1 


    ENSEMBL Gene Tree for WNK4 (if available)
    TreeFam Gene Tree for WNK4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for WNK4 gene
    WNK12  WNK22  NRBP12  NRBP22  WNK32  
    Selected SIMAP similar genes for WNK4 using alignment to 4 protein entries:     WNK4_HUMAN (see all proteins) (see all similar genes):
    CAMK2A    PKN2    BRAF    STK11    NEK6    NEK9
    ULK1    STK25    WNK2    BRSK2    MAPK3    NRBP2
    CDK3    CDK4    MARK4    STK17A    DAPK1    NEK7

    Find genes that share paralogs with WNK4           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for WNK4 (see all 577)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0413324
    A metastatic melanoma sample4--see VAR_0413322 P S mis40--------
    VAR_0175884
    Pseudohypoaldosteronism 2B (PHA2B)4--see VAR_0175882 E K mis40--------
    VAR_0175894
    Pseudohypoaldosteronism 2B (PHA2B)4--see VAR_0175892 D A mis40--------
    VAR_0175914
    Pseudohypoaldosteronism 2B (PHA2B)4--see VAR_0175912 R C mis40--------
    VAR_0175904
    Pseudohypoaldosteronism 2B (PHA2B)4--see VAR_0175902 Q E mis40--------
    VAR_0413304
    An ovarian mucinous carcinoma sample4--see VAR_0413302 E D mis40--------
    rs1378530931,2
    Cpathogenic141728864(+) AGCCAA/GAGGCA 2 K E mis10--------
    rs1378530941,2
    Cpathogenic141728871(+) GGCAGA/CCCAGC 2 D A mis10--------
    rs1378530921,2
    Cpathogenic141728873(+) CAGACC/GAGCAC 2 Q E mis10--------
    rs1378530951,2
    Cpathogenic141737623(+) CCAGCC/TGCCAG 2 R C mis10--------

    HapMap Linkage Disequilibrium report for WNK4 (40932649 - 40949084 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for WNK4:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv833450CNV Loss17160897
    nsv827998CNV Loss20364138
    nsv908257CNV Loss21882294
    esv33998OTHER Inversion15654335

    Human Gene Mutation Database (HGMD): WNK4
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing WNK4
    DNA2.0 Custom Variant and Variant Library Synthesis for WNK4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 601844   
    OMIM disorders: 614491  
    UniProtKB/Swiss-Prot: WNK4_HUMAN, Q96J92
  • Pseudohypoaldosteronism 2B (PHA2B) [MIM:614491]: An autosomal dominant disorder characterized by
    hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis, and correction of physiologic
    abnormalities by thiazide diuretics. Note=The disease is caused by mutations affecting the gene represented in
    this entry

  • 6 diseases for WNK4:    
    About MalaCards
    pseudohypoaldosteronism type iib    pseudohypoaldosteronism type ii    pseudohypoaldosteronism    liddle syndrome
    metabolic acidosis    essential hypertension

    4 diseases from the University of Copenhagen DISEASES database for WNK4:
    Pseudohypoaldosteronism     Hypertension     Liddle syndrome     Metabolic acidosis

    Find genes that share disorders with WNK4           About GenesLikeMe

    9 Novoseek inferred disease relationships for WNK4 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    pseudohypoaldosteronism 96.5 23 15300163 (2), 16173916 (1), 15796898 (1), 19016006 (1) (see all 21)
    gordon syndrome 95 6 19470686 (1), 18277144 (1), 16683163 (1), 15866321 (1) (see all 6)
    hyperkalemia 87.2 21 15696009 (2), 12515852 (2), 17360471 (2), 18695394 (1) (see all 15)
    hyperchloremia 77.6 1 12515852 (1)
    genetic hypertension 68.3 3 15309683 (1), 16501604 (1)
    essential hypertension 60.4 10 19340547 (4), 14967840 (2), 12719438 (1), 15866321 (1) (see all 6)
    metabolic acidosis 56 1 12515852 (1)
    hypertension arterial 31.7 2 16173916 (1), 18701621 (1)
    hypotension 1.69 2 15309683 (1)

    Genetic Association Database (GAD): WNK4
    Human Genome Epidemiology (HuGE) Navigator: WNK4 (12 documents)

    Export disorders for WNK4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for WNK4 gene, integrated from 10 sources (see all 108):
    (articles sorted by number of sources associating them with WNK4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Association of Ala589Ser polymorphism of WNK4 gene with essential hypertension in a high-risk Chinese population. (PubMed id 19340547)1, 4, 9 Sun Z.J....Zhao Y.Y. (J Physiol Sci 2009)
    2. Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population. (PubMed id 15309683)1, 4, 9 Kokubo Y....Miyata T. (J. Hum. Genet. 2004)
    3. Genetic variants of WNK4 in whites and African Americans with hypertension. (PubMed id 12719438)1, 4, 9 Erlich P.M....DeStefano A.L. (Hypertension 2003)
    4. WNK4 intron 10 polymorphism is not associated with hypertension. (PubMed id 14967840)1, 4, 9 Speirs H.J. and Morris B.J. (Hypertension 2004)
    5. The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics. (PubMed id 15824464)1, 4, 9 Matayoshi T....Kawano Y. (Hypertens. Res. 2004)
    6. Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension. (PubMed id 14616768)1, 4, 9 Benjafield A.V....Morris B.J. (Clin. Genet. 2003)
    7. The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. (PubMed id 23387299)1, 2 Ohta A....Kurz T. (Biochem. J. 2013)
    8. Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4. (PubMed id 23576762)1, 2 Shibata S....Lifton R.P. (Proc. Natl. Acad. Sci. U.S.A. 2013)
    9. Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation. (PubMed id 23665031)1, 2 Wu G. and Peng J.B. (FEBS Lett. 2013)
    10. Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension. (PubMed id 23453970)1, 2 Wakabayashi M....Uchida S. (Cell Rep 2013)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 65266 HGNC: 14544 AceView: PRKWNK4 Ensembl:ENSG00000126562 euGenes: HUgn65266
    ECgene: WNK4 H-InvDB: WNK4

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for WNK4 Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=WNK4[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for WNK4 gene:
    Search GeneIP for patents involving WNK4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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